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SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

Oncogene volume 29, pages 5511–5522 (2010)Cite this article

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Abstract

The E1B-55K product from human adenovirus is a substrate of the small ubiquitin-related modifier (SUMO)-conjugation system. SUMOylation of E1B-55K is required to transform primary mammalian cells in cooperation with adenovirus E1A and to repress p53 tumour suppressor functions. The biochemical consequences of SUMO1 conjugation of 55K have so far remained elusive. Here, we report that E1B-55K physically interacts with different isoforms of the tumour suppressor protein promyelocytic leukaemia (PML). We show that E1B-55K binds to PML isoforms IV and V in a SUMO1-dependent and -independent manner. Interaction with PML-IV promotes the localization of 55K to PML-containing subnuclear structures (PML-NBs). In virus-infected cells, this process is negatively regulated by other viral proteins, indicating that binding to PML is controlled through reversible SUMOylation in a timely coordinated manner. These results together with earlier work are consistent with the idea that SUMOylation regulates targeting of E1B-55K to PML-NBs, known to control transcriptional regulation, tumour suppression, DNA repair and apoptosis. Furthermore, they suggest that SUMO1-dependent modulation of p53-dependent growth suppression through E1B-55K PML-IV interaction has a key role in adenovirus-mediated cell transformation.

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References

  • Ascoli CA, Maul GG . (1991). Identification of a novel nuclear domain. J Cell Biol 112: 785–795.

    CAS  PubMed  Google Scholar 

  • Baker A, Rohleder KJ, Hanakahi LA, Ketner G . (2007). Adenovirus E4 34k and E1b 55k oncoproteins target host DNA ligase IV for proteasomal degradation. J Virol 81: 7034–7040.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bischof O, Kim SH, Irving J, Beresten S, Ellis NA, Campisi J . (2001). Regulation and localization of the Bloom syndrome protein in response to DNA damage. J Cell Biol 153: 367–380.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bischof O, Kirsh O, Pearson M, Itahana K, Pelicci PG, Dejean A . (2002). Deconstructing PML-induced premature senescence. EMBO J 21: 3358–3369.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Borden KL, Culjkovic B . (2009). Perspectives in PML: a unifying framework for PML function. Front Biosci 14: 497–509.

    CAS  Google Scholar 

  • Carbone R, Pearson M, Minucci S, Pelicci PG . (2002). PML NBs associate with the hMre11 complex and p53 at sites of irradiation induced DNA damage. Oncogene 21: 1633–1640.

    CAS  PubMed  Google Scholar 

  • Carvalho T, Seeler JS, Öhman K, Jordan P, Pettersson U, Akusjärvi G et al. (1995). Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies. J Cell Biol 131: 45–56.

    CAS  PubMed  Google Scholar 

  • Cerec V, Glaise D, Garnier D, Morosan S, Turlin B, Drenou B et al. (2007). Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor. Hepatology 45: 957–967.

    CAS  PubMed  Google Scholar 

  • Chang KS, Stass SA, Chu DT, Deaven LL, Trujillo JM, Freireich EJ . (1992). Characterization of a fusion cDNA (RARA/myl) transcribed from the t(15;17) translocation breakpoint in acute promyelocytic leukemia. Mol Cell Biol 12: 800–810.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Condemine W, Takahashi Y, Zhu J, Puvion-Dutilleul F, Guegan S, Janin A et al. (2006). Characterization of endogenous human promyelocytic leukemia isoforms. Cancer Res 66: 6192–6198.

    CAS  PubMed  Google Scholar 

  • Dallaire F, Blanchette P, Groitl P, Dobner T, Branton PE . (2009). Identification of integrin alpha3 as a new substrate of the adenovirus E4orf6/E1B 55-kilodalton E3 ubiquitin ligase complex. J Virol 83: 5329–5338.

    CAS  PubMed  PubMed Central  Google Scholar 

  • de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A . (1991). The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66: 675–684.

    CAS  PubMed  Google Scholar 

  • Dellaire G, Bazett-Jones DP . (2004). PML nuclear bodies: dynamic sensors of DNA damage and cellular stress. Bioessays 26: 963–977.

    CAS  PubMed  Google Scholar 

  • Dobner T, Kzhyshkowska J . (2001). Nuclear export of adenovirus RNA. Curr Top Microbiol Immunol 259: 25–54.

    CAS  PubMed  Google Scholar 

  • Doucas V, Ishov AM, Romo A, Juguilon H, Weitzman MD, Evans RM et al. (1996). Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure. Genes Dev 10: 196–207.

    CAS  PubMed  Google Scholar 

  • Dyck JA, Maul GG, Miller Jr WH, Chen JD, Kakizuka A, Evans RM . (1994). A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell 76: 333–343.

    CAS  PubMed  Google Scholar 

  • Endter C, Hartl B, Spruss T, Hauber J, Dobner T . (2005). Blockage of CRM1-dependent nuclear export of the adenovirus type 5 early region 1B 55-kDa protein augments oncogenic transformation of primary rat cells. Oncogene 24: 55–64.

    CAS  PubMed  Google Scholar 

  • Endter C, Kzhyshkowska J, Stauber R, Dobner T . (2001). SUMO-1 modification is required for transformation by adenovirus type 5 early region 1B 55-kDa oncoprotein. Proc Natl Acad Sci USA 98: 11312–11317.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Everett RD . (2001). DNA viruses and viral proteins that interact with PML nuclear bodies. Oncogene 20: 7266–7273.

    CAS  PubMed  Google Scholar 

  • Everett RD, Chelbi-Alix MK . (2007). PML and PML nuclear bodies: implications in antiviral defence. Biochimie 89: 819–830.

    CAS  PubMed  Google Scholar 

  • Everett RD, Parada C, Gripon P, Sirma H, Orr A . (2007). Replication of ICP0-null mutant herpes simplex virus type 1 is restricted by both PML and Sp100. J Virol 82: 2661–2672.

    PubMed  PubMed Central  Google Scholar 

  • Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW . (2000). PML is induced by oncogenic ras and promotes premature senescence. Genes Dev 14: 2015–2027.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K et al. (2000). Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J 19: 6185–6195.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goddard AD, Borrow J, Solomon E . (1992). A previously uncharacterized gene, PML, is fused to the retinoic acid receptor alpha gene in acute promyelocytic leukaemia. Leukemia 6 (Suppl 3): 117S–119S.

    PubMed  Google Scholar 

  • Goddard AD, Yuan JQ, Fairbairn L, Dexter M, Borrow J, Kozak C et al. (1995). Cloning of the murine homolog of the leukemia-associated PML gene. Mamm Genome 6: 732–737.

    CAS  PubMed  Google Scholar 

  • Graham FL, Smiley J, Russel WC, Nairn R . (1977). Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36: 59–72.

    CAS  PubMed  Google Scholar 

  • Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I et al. (2002). Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci USA 99: 15655–15660.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Groitl P, Dobner T . (2007). Construction of adenovirus type 5 early region 1 and 4 virus mutants. Methods Mol Med 130: 29–39.

    CAS  PubMed  Google Scholar 

  • Guccione E, Lethbridge KJ, Killick N, Leppard KN, Banks L . (2004). HPV E6 proteins interact with specific PML isoforms and allow distinctions to be made between different POD structures. Oncogene 23: 4662–4672.

    CAS  PubMed  Google Scholar 

  • Gurrieri C, Capodieci P, Bernardi R, Scaglioni PP, Nafa K, Rush LJ et al. (2004). Loss of the tumor suppressor PML in human cancers of multiple histologic origins. J Natl Cancer Inst 96: 269–279.

    CAS  PubMed  Google Scholar 

  • Härtl B, Zeller T, Blanchette P, Kremmer E, Dobner T . (2008). Adenovirus type 5 early region 1B 55-kDa oncoprotein can promote cell transformation by a mechanism independent from blocking p53-activated transcription. Oncogene 27: 3673–3684.

    PubMed  Google Scholar 

  • Hay RT . (2005). SUMO: a history of modification. Mol Cell 18: 1–12.

    CAS  PubMed  Google Scholar 

  • Herrmann F, Lee J, Bedford MT, Fackelmayer FO . (2005). Dynamics of human protein arginine methyltransferase 1(PRMT1) in vivo. J Biol Chem 280: 38005–38010.

    CAS  PubMed  Google Scholar 

  • Hofmann TG, Will H . (2003). Body language: the function of PML nuclear bodies in apoptosis regulation. Cell Death Differ 10: 1290–1299.

    CAS  PubMed  Google Scholar 

  • Hoppe A, Beech SJ, Dimmock J, Leppard KN . (2006). Interaction of the adenovirus type 5 E4 Orf3 protein with promyelocytic leukemia protein isoform II is required for ND10 disruption. J Virol 80: 3042–3049.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen K, Shiels C, Freemont PS . (2001). PML protein isoforms and the RBCC/TRIM motif. Oncogene 20: 7223–7233.

    CAS  PubMed  Google Scholar 

  • Kakizuka A, Miller Jr WH, Umesono K, Warrell Jr RP, Frankel SR, Murty VV et al. (1991). Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 66: 663–674.

    CAS  PubMed  Google Scholar 

  • Kao CC, Yew PR, Berk AJ . (1990). Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology 179: 806–814.

    CAS  PubMed  Google Scholar 

  • Kastner P, Perez A, Lutz Y, Rochette Egly C, Gaub MP, Durand B et al. (1992). Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. EMBO J 11: 629–642.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kindsmüller K, Groitl P, Härtl B, Blanchette P, Hauber J, Dobner T . (2007). Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation. Proc Natl Acad Sci USA 104: 6684–6689.

    PubMed  PubMed Central  Google Scholar 

  • Kindsmüller K, Schreiner S, Leinenkugel F, Groitl P, Kremmer E, Dobner T . (2009). A 49-kilodalton isoform of the adenovirus type 5 early region 1B 55-kilodalton protein is sufficient to support virus replication. J Virol 83: 9045–9056.

    PubMed  PubMed Central  Google Scholar 

  • Koken MH, Linares-Cruz G, Quignon F, Viron A, Chelbi-Alix MK, Sobczak-Thèpot J et al. (1995). The PML growth-suppressor has an altered expression in human oncogenesis. Oncogene 10: 1315–1324.

    CAS  PubMed  Google Scholar 

  • Koken MH, Puvion-Dutilleul F, Guillemin MC, Viron A, Linares-Cruz G, Stuurman N et al. (1994). The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J 13: 1073–1083.

    CAS  PubMed  PubMed Central  Google Scholar 

  • König C, Roth J, Dobbelstein M . (1999). Adenovirus type 5 E4orf3 protein relieves p53 inhibition by E1B-55-kilodalton protein. J Virol 73: 2253–2262.

    PubMed  PubMed Central  Google Scholar 

  • Krätzer F, Rosorius O, Heger P, Hirschmann N, Dobner T, Hauber J et al. (2000). The adenovirus type 5 E1B-55k oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2. Oncogene 19: 850–857.

    PubMed  Google Scholar 

  • Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky A et al. (2001). Role of promyelocytic leukemia (PML) SUMOlation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. J Exp Med 193: 1361–1371.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S et al. (2002). Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21: 2383–2396.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lawrence JM, Singhal S, Bhatia B, Keegan DJ, Reh TA, Luthert PJ et al. (2007). MIO-M1 cells and similar Müller glial cell lines derived from adult human retina exhibit neural stem cell characteristics. Stem Cells 25: 2033–2043.

    CAS  PubMed  Google Scholar 

  • Lee K, Zerivitz K, Akusjärvi G . (1995). Small-Scale Preparation of Nuclear Extracts from Mammalian Cells in Cell Biology. SpringerProtocols: London.

    Google Scholar 

  • Leppard KN, Emmott E, Cortese MS, Rich T . (2009). Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein nuclear domains for disruption via a sequence in PML isoform II that is predicted as a protein interaction site by bioinformatic analysis. J Gen Virol 90: 95–104.

    CAS  PubMed  Google Scholar 

  • Lethbridge KJ, Scott GE, Leppard KN . (2003). Nuclear matrix localization and SUMO-1 modification of adenovirus type 5 E1b 55K protein are controlled by E4 Orf6 protein. J Gen Virol 84: 259–268.

    CAS  PubMed  Google Scholar 

  • Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ et al. (2000). Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol 20: 1784–1796.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Limb GA, Salt TE, Munro PMG, Moss SE, Khaw PT . (2002). In vitro characterization of a spontaneously immortalized human Müller cell line (MIO-M1). Invest Ophthalmol Vis Sci 43: 864–869.

    PubMed  Google Scholar 

  • Lukashchuk V, Everett RD . (2010). Regulation of ICP0 null mutant HSV-1 infection by ND10 components ATRX and hDaxx. J Virol 84: 4026–4040.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin ME, Berk AJ . (1998). Adenovirus E1B 55K represses p53 activation in vitro. J Virol 72: 3146–3154.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin ME, Berk AJ . (1999). Corepressor required for adenovirus E1B 55,000-molecular-weight protein repression of basal transcription. Mol Cell Biol 19: 3403–3414.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Melnick A, Fruchtman S, Zelent A, Liu M, Huang Q, Boczkowska B et al. (1999). Identification of novel chromosomal rearrangements in acute myelogenous leukemia involving loci on chromosome 2p23, 15q22 and 17q21. Leukemia 13: 1534–1538.

    CAS  PubMed  Google Scholar 

  • Melnick A, Licht JD . (1999). Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 93: 3167–3215.

    CAS  PubMed  Google Scholar 

  • Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner HK et al. (1992). p53 gene mutations in non-small-lung cell cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene 7: 171–180.

    CAS  PubMed  Google Scholar 

  • Müller S, Dobner T . (2008). The adenovirus E1B-55K oncoprotein induces SUMO modification of p53. Cell Cycle 7: 754–758.

    PubMed  Google Scholar 

  • Nevels M, Rubenwolf S, Spruss T, Wolf H, Dobner T . (1997). The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function. Proc Natl Acad Sci USA 94: 1206–1211.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nevels M, Täuber B, Spruss T, Wolf H, Dobner T . (2001). Hit-and-run’ transformation by adenovirus oncogenes. J Virol 75: 3089–3094.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ornelles DA, Shenk T . (1991). Localization of the adenovirus early region 1B 55-kilodalton protein during lytic infection: association with nuclear viral inclusions requires the early region 4 34-kilodalton protein. J Virol 65: 424–429.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pandolfi PP, Alcalay M, Fagioli M, Zangrilli D, Mencarelli A, Diverio D et al. (1992). Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia. EMBO J 11: 1397–1407.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S et al. (2000). PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406: 207–210.

    CAS  PubMed  Google Scholar 

  • Ponten J, Saksela E . (1967). Two established in vitro cell lines from human mesenchymal tumours. Int J Cancer 2: 434–447.

    CAS  PubMed  Google Scholar 

  • Puvion-Dutilleul F, Chelbi-Alix MK, Koken M, Quignon F, Puvion E, de The H . (1995). Adenovirus infection induces rearrangements in the intranuclear distribution of the nuclear body-associated PML protein. Exp Cell Res 218: 9–16.

    CAS  PubMed  Google Scholar 

  • Querido E, Morisson MR, Chu-Pham-Dang H, Thirlwell SW, Boivin D, Branton PE . (2001). Identification of three functions of the adenovirus E4orf6 protein that mediate p53 degradation by the E4orf6-E1B55K complex. J Virol 75: 699–709.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Regad T, Bellodi C, Nicotera P, Salomoni P . (2009). The tumor suppressor Pml regulates cell fate in the developing neocortex. Nat Neurosci 12: 132–140.

    CAS  PubMed  Google Scholar 

  • Salomoni P . (2009). Stemming out of a new PML era? Cell Death Differ 16: 1083–1092.

    CAS  PubMed  Google Scholar 

  • Salomoni P, Ferguson BJ, Wyllie AH, Rich T . (2008). New insights into the role of PML in tumour suppression. Cell Res 18: 622–640.

    CAS  PubMed  Google Scholar 

  • Salomoni P, Pandolfi PP . (2002). The role of PML in tumor suppression. Cell 108: 165–170.

    CAS  PubMed  Google Scholar 

  • Sarnow P, Ho YS, Williams J, Levine AJ . (1982a). Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell 28: 387–394.

    CAS  PubMed  Google Scholar 

  • Sarnow P, Sullivan CA, Levine AJ . (1982b). A monoclonal antibody detecting the adenovirus type 5-E1b-58Kd tumor antigen: characterization of the E1b-58Kd tumor antigen in adenovirus-infected and -transformed cells. Virology 120: 510–517.

    CAS  PubMed  Google Scholar 

  • Scaglioni PP, Yung TM, Cai LF, Erdjument-Bromage H, Kaufman AJ, Singh B et al. (2006). A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell 126: 269–283.

    CAS  PubMed  Google Scholar 

  • Schreck KC, Gaiano N . (2009). PML: a tumor suppressor essential for neocortical development. Nat Neurosci 12: 108–110.

    CAS  PubMed  Google Scholar 

  • Shen TH, Lin HK, Scaglioni PP, Yung TM, Pandolfi PP . (2006). The mechanisms of PML-nuclear body formation. Mol Cell 24: 331–339.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sieber T, Dobner T . (2007). Adenovirus type 5 early region 1B 156R protein promotes cell transformation independently of repression of p53-stimulated transcription. J Virol 81: 95–105.

    CAS  PubMed  Google Scholar 

  • Stracker TH, Carson CT, Weitzman MD . (2002). Adenovirus oncoproteins inactivate the Mre11 Rad50 NBS1 DNA repair complex. Nature 418: 348–352.

    CAS  PubMed  Google Scholar 

  • Stracker TH, Lee DV, Carson CT, Araujo FD, Ornelles DA, Weitzman MD . (2005). Serotype-specific reorganization of the Mre11 complex by adenoviral E4orf3 proteins. J Virol 79: 6664–6673.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stuurman N, de Graaf A, Floore A, Josso A, Humbel B, de Jong L et al. (1992). A monoclonal antibody recognizing nuclear matrix-associated nuclear bodies. J Cell Sci 101: 773–784.

    PubMed  Google Scholar 

  • Takahashi Y, Lallemand-Breitenbach V, Zhu J, de The H . (2004). PML nuclear bodies and apoptosis. Oncogene 23: 2819–2824.

    CAS  PubMed  Google Scholar 

  • Tavalai N, Stamminger T . (2008). New insights into the role of the subnuclear structure ND10 for viral infection. Biochim Biophys Acta 1783: 2207–2221.

    CAS  PubMed  Google Scholar 

  • Torok D, Ching RW, Bazett-Jones DP . (2009). PML nuclear bodies as sites of epigenetic regulation. Front Biosci 14: 1325–1336.

    CAS  Google Scholar 

  • Ullman AJ, Hearing P . (2008). Cellular proteins PML and Daxx mediate an innate antiviral defense antagonized by the adenovirus E4 ORF3 protein. J Virol 82: 7325–7335.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ullman AJ, Reich NC, Hearing P . (2007). Adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral response. J Virol 81: 4744–4752.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Van Damme E, Laukens K, Dang TH, Van Ostade X . (2010). A manually curated network of the PML nuclear body interactome reveals an important role for PML-NBs in SUMOylation dynamics. Int J Biol Sci 6: 51–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Fonseca M et al. (1994). Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell 76: 345–356.

    CAS  PubMed  Google Scholar 

  • Yew PR, Liu X, Berk AJ . (1994). Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev 8: 190–202.

    CAS  PubMed  Google Scholar 

  • Younghusband HB . (1985). An association between replicating adenovirus DNA and the nuclear matrix of infected HeLa cells. Can J Biochem Cell Biol 63: 654–660.

    CAS  PubMed  Google Scholar 

  • Zantema A, Fransen JA, Davis-Olivier A, Ramaekers FC, Vooijs GP, DeLeys B et al. (1985a). Localization of the E1B proteins of adenovirus 5 in transformed cells, as revealed by interaction with monoclonal antibodies. Virology 142: 44–58.

    CAS  PubMed  Google Scholar 

  • Zantema A, Schrier PI, Davis-Olivier A, van Laar T, Vaessen RT, van der EA . (1985b). Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells. Mol Cell Biol 5: 3084–3091.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong S, Salomoni P, Pandolfi PP . (2000). The transcriptional role of PML and the nuclear body. Nat Cell Biol 2: E85–E90.

    CAS  PubMed  Google Scholar 

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Acknowledgements

PW was supported by grants from the ‘Studienstiftung des Deutschen Volkes e.V.’, Ahrstraße 41, 53175 Bonn, Germany. We thank Philippe Gripon for providing the described HepaRG cell line and Roel van Driel/Ineke van der Kraan for the 5E10 antibody. The Heinrich-Pette-Institute is supported by the ‘Freie und Hansestadt Hamburg’ and the ‘Bundesministerium für Gesundheit’. This work was supported by grants from the ‘Deutsche Forschungsgemeinschaft (DFG)’ and by the ‘Stiftung für neurovirale Erkrankungen’ to HS.

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  1. P Wimmer and S Schreiner: These two co-first authors contributed equally to this work.

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  1. Department of Molecular Virology, Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany

    P Wimmer, S Schreiner, P Groitl & T Dobner

  2. MRC Virology Unit, Institute of Virology, Scotland, UK

    R D Everett

  3. Institute of Pathology, University Medical Center, Hamburg, Germany

    H Sirma

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Wimmer, P., Schreiner, S., Everett, R. et al. SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML. Oncogene 29, 5511–5522 (2010). https://doi.org/10.1038/onc.2010.284

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